The central objective of this project is to approach some of the individual steps of potential importance in the ontogeny of host defenses, which permits correlation of results and determination of relative importance among the various systems. There are four basic components in the proposal - Project I: This seeks to characterize the ontogeny of the functional integrity of the phagocytic cells (polymorphonuclear leukocytes (PMNs) and mononuclear leukocytes (MNLs)). Project II: This seeks to characterize the ontogeny of the fetal T and B cell systems with particular reference to their functional capabilities to influence phagocyte functions. Project III: This seeks to probe the ontogenesis of a number of leukocyte metabolic functions in the fetal sheep model and to correlate them with the development of the activity of glycolytic enzymes, hexosemonophosphate shunt activity, hydrogen peroxide generation and superoxide production at various stages of fetal ovine development. In addition, intracellular levels of lysosomal enzymes will be studied as will the ability of fetal phagocytes to release these enzymes upon stimulation. Project IV: This uses the fetal lamb as an experimental model to investigate the effects of development of the above three areas in aiding the fetal lamb in withstanding transplacental or direct infection with the ovine pathogen, blue-tongue virus.